Exposure of cells to ultraviolet light, ionizing radiation and certain chemicals can lead to cell death, mutation or malignant transformation. All these agents produce damage to the genetic material. Ionizing radiation and certain chemicals, mutagens and carcinogens, are of particular importance to the Health Sciences since they are at the same time dangerous potential "pollutants" of our environment and important tools in the treatment of many diseases, in particular, of cancer. The major aim in our program is to identify and characterize DNA excision repair pathways in normal and diseased human cells. The excision of damage produced in DNA by ultraviolet light, ionizing radiation and the chemical carcinogens ethylnitrosourea and benz(a)pyrene is being investigated. These studies are being carried out in intact mammalian cells and in in vitro component systems. In the in vitro experiments whole cell sonicates or nuclear preparations from cultured human skin fibroblasts and exogenous, damage DNA substrates is being used in part of our experiments. The excision capacity of preparations from normal cells are compared to preparations from Fanconi's Anemia and Xeroderma pigmentosum are autosomal recessive diseases in man with increased frequencies for the development of cancer. Excision competition studies are being carried out with cells or DNA substrates containing different classes of DNA lesions. The goal in these studies is to distinguish different excision pathways and to derive a functionally meaningful classification of DNA base damage. BIBLIOGRAPHIC REFERENCES: J. Remsen and P. Cerutti - Gamma-ray Excision Repair Deficiency in Fanconi's Anemia Skin Fibroblasts. Proc. Natl. Acad. Sci. 73, 2419 (1976). P.V. Hariharan and P.A. Cerutti -Excision of ultraviolet and gamma-ray products of the 5,6-dihydroxydihydrothymine type by nuclear preparations of Xeroderma pigmentosum cells. Biochem. Biophys. Acta 447, 375 (1976).